Standardized versus individualized growth hormone treatment of short children born small for gestational age: Effects on short-term and longterm efficacy, long-term psychosocial development, glucose metabolism and body composition.

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 300

Inclusion Criteria

• Children born with a birth length and/or weight <-2 SD for gestational age (Usher and McLean)
• Short stature defined as height SD score <-2.5 according to the Dutch National Growth References of 1997
• Height of <=1 SD score below target height SD score (TH SDS).
• Height velocity (cm/year) for chronological age <=0 SDS in prepubertal children
• Chronological age at start of treatment between 4 and 11 years for boys and between 4 and 9 years for girls
• Bone age (G&P) <=13 years for girls and <=15 years for boys
• Well documented growth data from birth up to 2 years and at least 1 year before the start of the study.
• Informed consent.

Exclusion Criteria

• Syndromes (except for Silver Russell Syndrome), chromosomal abnormalities and serious dysmorphic symptoms suggestive for a syndrome that has not yet been described
• Severe psychomotor retardation according to the DSM IV
• Complicated neonatal period, including signs of severe asphyxia (defined as an Apgar score <3 after 5 minutes, severe sepsis with multiple organ failure (MOF), long term artificial ventilation and oxygen supply and/or bronchopulmonary dysplasia
• Celiac disease and other chronic or serious diseases of the gastro-intestinal tract, heart, genito-urinary tract, liver, lungs, skeleton or central nervous system, or chronic or recurrent major infectious diseases, nutritional and/or vitamin deficiencies
• Any endocrine or metabolic disorder such as diabetes mellitus, diabetes insipidus, hypothyroidism, or inborn errors of metabolism, except for growth hormone deficiency (GHD)
• Genetic alterations (e.g. mutations, deletions) in the IGF-I receptor gene
• Medications or interventions during the previous 6 months that might have interfered with growth, such as corticosteroids (including high dose of corticosteroids inhalation), sex steroids, growth hormone, or major surgery (particularly of the spine and extremities)
• Use of medication that might interfere with growth during GH therapy, such as corticosteroids and sex steroids
• Active or treated malignancy or increased risk of leukaemia
• Serious suspicion of psychosocial dwarfism (emotional deprivation)
• Expected non-compliance

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary objectives:<br /><br>• To assess the effect of individualizing the growth hormone dose versus<br /><br>standard treatment with 1 mg/m2/day on adult height SDS.<br /><br>• To study whether treatment with individualizing the growth hormone dose<br /><br>results in comparable adult height SDS as standard treatment with 1 mg/m2/day<br /><br>(non-inferiorty) </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary objectives<br /><br>• To assess the effect of individualizing the growth hormone dose versus<br /><br>standard treatment with 1 mg/m2/day on the first and five year growth response.<br /><br>• To assess the long term safety of growth hormone therapy on glucose<br /><br>metabolism and body composition.<br /><br>• To determine the effect of growth hormone therapy on psychosocial and<br /><br>neurological development, and intelligence. </p><br>